October 14, 2005

Brain tumor treatment showing promise

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Dennis Hallahan, M.D.

Brain tumor treatment showing promise

Glioblastoma multiforme is the medical name given to a very rare brain tumor that doctors often say is incurable.

In the past, patients with the aggressive tumor were given little chance at any length of survival, but now, experts at the Vanderbilt-Ingram Cancer Center say they've uncovered what could lead to a promising new way to target and fight glioblastomas.

The new weapon is Gleevec, a molecularly targeted cancer drug made by Novartis that has been used to treat several other types of cancer.

Drugs such as this zero in on molecular targets or specific cancer cells, thereby sparing surrounding normal, healthy tissue. They have been used to treat breast cancer, colon cancer, lung cancer, gastrointestinal stromal tumors and chronic myeloid leukemia.

Dennis Hallahan, M.D., professor and chair of the Vanderbilt Center for Radiation Oncology at the Vanderbilt-Ingram Cancer Center, is now studying the use of Gleevec to treat glioblastomas.

“In other cancers, molecular targeted therapy is very specific and only inhibits a single molecule. We wanted to determine whether a non-specific molecule inhibitor could change how glioblastomas respond to radiation therapy,” said Hallahan.

The early answer is yes. Hallahan said pre-clinical trials using mice showed Gleevec inhibited the growth of glioblastoma.

“It inhibits the PDGF receptor, or platelet derived growth factor, very well. It worked so well in pre-clinical models that I'm hopeful we have something that can help patients,” he added.

Hallahan is gearing up for a Phase I trial involving men and women diagnosed with incurable glioblastomas. The study would investigate whether patients can tolerate Gleevec while undergoing radiation to shrink the brain tumor.

So what, if any, is the potential downside? Hallahan said using Gleevec in treating patients with glioblastomas could sensitize normal brain tissue to radiation, but he said it has not proven to be the case in the other cancers being treated with the same combination.

Hallahan, like many other experts, predicts molecularly targeted therapies like this are the future of cancer treatment.

“This is the way we'll be treating cancer in the years to come. Each patient will have specific inhibitors selected for treatment of their cancer and we'll treat each patient individually to minimize side effects and optimize cure rates.”

Hallahan is preparing to share his findings at the annual meeting of the American Society for Therapeutic Radiation and Oncology in Denver later this month. He and other colleagues at Vanderbilt-Ingram will present 20 abstracts chosen by the national organization for special presentations. Other abstracts being presented include ongoing research at Vanderbilt-Ingram to determine whether lithium may protect against memory deficits that result from radiation therapy, and a new study testing an investigational drug that Hallahan said could increase the effectiveness of radiation treatment and may also offer yet another option for patients with glioblastomas in the future.

“This investigational drug, IC87361 as it is known, is a molecular-targeted therapy that inhibits a DNA repair enzyme called DNA dependent protein kinase,” said Hallahan. “Cancer DNA is damaged by radiation and cancer cells are very efficient at repairing DNA damage and allowing cells to continue to divide.”

In Hallahan's pre-clinical studies in mice, the investigational drug, administered through an IV line, proved to inhibit DNA repair during radiation, and in turn, made radiation treatment more effective at killing the cancer cells. “Early work has shown this drug is very effective in improving efficacy of radiation therapy in lung cancer and glioblastoma,” said Hallahan. “I would say it is three times more effective at improving radiation-induced killing of cancer cells,” he added.

Hallahan said this study could reach the next phase of testing in human patients in two years.